This R01 application proposes to use functional neuroimaging with human subjects to elucidate the role of prefrontal-amygdala circuitry in the processing of facial expressions that predict different social outcomes. Presentations of facial expressions of emotion in neuroimaging studies have proven particularly robust stimuli for activating amygdala and prefrontal regions involved in processing biologically-relevant social cues. Further, these tasks have proven useful for revealing aberrant brain activation patterns in patients with various emotional disorders (e.g., anxiety, depression). Here we propose to further develop facial expression tasks for use with specific psychopathological disorders. The utility of this work is that it will provide for a better understanding of the basic rules that determine amygdala response (Aim 1), allow us to better understand how the amygdala interacts with reciprocally connected prefrontal areas when such expressions are encountered (Aim 2) and tie this social/emotional human work to the greater Pavlovian conditioning work, which shows particular promise for elucidating the neural substrates of fear learning and its aberrations in anxiety disorders (Aim 3). The experiments proposed here are critical for establishing an understanding of the normal pattern of human brain responsivity to important social cues in order to allow future developmental research (i.e., with children and adolescents) as well as direct translation to clinical populations. An area of the brain called the amygdala is particularly responsive to the facial expressions of others and has been shown to exhibit exaggerated reactivity to the facial expression of fear in subjects with anxiety disorders. This may, in part, underlie the symptoms of increased vigilance and hyper-reactivity to potential threat that plague individuals with anxiety disorders. The studies proposed here will further our understanding of these brain responses to facial expressions and offer improved human brain imaging tasks for future study of the brain responses that underlie anxiety disorders. [unreadable] [unreadable] [unreadable]